Cardiotrophin-1 stimulates lipolysis through the regulation of main adipose tissue lipases[S]

• Main Authors: Miguel López-Yoldi, Marta Fernández-Galilea, Laura M. Laiglesia, Eduardo Larequi, Jesús Prieto, J. Alfredo Martínez, Matilde Bustos, Maria J. Moreno-Aliaga
• Format: Article
• Language: English
• Published: Elsevier 2014-12-01
• Series: Journal of Lipid Research
• Subjects: adipocytes; adipose triglyceride lipase; cell signaling; cytokines; hormone-sensitive lipase; obesity
• Online Access: http://www.sciencedirect.com/science/article/pii/S002222752036702X

Cardiotrophin-1 (CT-1) is a cytokine with antiobesity properties and with a role in lipid metabolism regulation and adipose tissue function. The aim of this study was to analyze the molecular mechanisms involved in the lipolytic actions of CT-1 in adipocytes. Recombinant CT-1 (rCT-1) effects on the main proteins and signaling pathways involved in the regulation of lipolysis were evaluated in 3T3-L1 adipocytes and in mice. rCT-1 treatment stimulated basal glycerol release in a concentration- and time-dependent manner in 3T3-L1 adipocytes. rCT-1 (20 ng/ml for 24 h) raised cAMP levels, and in parallel increased protein kinase (PK)A-mediated phosphorylation of perilipin and hormone sensitive lipase (HSL) at Ser660. siRNA knock-down of HSL or PKA, as well as pretreatment with the PKA inhibitor H89, blunted the CT-1-induced lipolysis, suggesting that the lipolytic action of CT-1 in adipocytes is mainly mediated by activation of HSL through the PKA pathway. In ob/ob mice, acute rCT-1 treatment also promoted PKA-mediated phosphorylation of perilipin and HSL at Ser660 and Ser563, and increased adipose triglyceride lipase (desnutrin) content in adipose tissue. These results showed that the ability of CT-1 to regulate the activity of the main lipases underlies the lipolytic action of this cytokine in vitro and in vivo, and could contribute to CT-1 antiobesity effects.